The long-range objective of the proposed research is to understand the biochemical mechanism by which calcium fluxes are regulated across cardiac sarcoplasmic reticulum membranes. We have obtained preliminary evidence to indicate that calmodulin stimulates calcium transport by an increase in the phosphorylation of phospholamban. This is a 22,000 dalton protein that we have previously shown to be phosphorylated by cyclic AMP-dependent protein kinase. The proposed research will elucidate the biochemical mechanism of the dual control of calcium transport by calmodulin and cyclic AMP-dependent protein kinase. Studies will be carried out in vitro with isolated canine cardiac sarcoplasmic reticulum.